Systemic administration of interleukin-12 can restore the anti-tumor potential of B16 melanoma-draining lymph node cells impaired at a late tumor-bearing state.
We investigated the effect of the systemic administration of interleukin (IL)-12 on the anti-tumor potential of tumor-draining lymph nodes (LNs). Tumor-draining LN cells on day 10 after s.c. inoculation of B16 melanoma showed a significant anti-tumor effect against established pulmonary metastases after in vitro expansion, whereas those on either day 20 or 30 exhibited an impaired anti-tumor potential. However, i.p. injections of IL-12 (0.5 microg) on days 18, 20 and 22 significantly increased the total number of tumor-draining LN cells on day 24 and, furthermore, restored their anti-tumor potential after in vitro expansion. In addition, i.p. injection of IL-12 (0.1 microg) on days 20, 22, 24, 26 and 28 significantly suppressed the growth of s.c.-inoculated B16 melanoma and finally cured the tumors in 6 of 12 mice (50%), whereas dissection of the tumor-draining LNs on day 18, prior to the IL-12 treatment, decreased both the IL-12-induced anti-tumor effect and the percentage of cured mice (8.3%). Cured mice acquired a specific protective immunity. Collectively, our results indicate that the systemic administration of IL-12 can restore the immunotherapeutic potential of tumor-draining LNs, which was impaired at the late tumor-bearing state, and that the IL-12-induced systemic anti-tumor activity is preceded by the restoration of an anti-tumor response in tumor-draining LNs.
Harada
M
M
Department of Virology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan. harada@bioreg.kyushu-u.ac.jp
Tamada
K
K
Abe
K
K
Li
T
T
Onoe
Y
Y
Tada
H
H
Takenoyama
M
M
Yasumoto
K
K
Kimura
G
G
Nomoto
K
K
D000818:Animals; D005260:Female; D016219:Immunotherapy, Adoptive; D018664:Interleukin-12 / Q000494:pharmacology*; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D016399:Lymphoma, T-Cell / Q000628:therapy; D008546:Melanoma, Experimental / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation
D018664:Interleukin-12